title: Measurements of the pons as a biomarker of progression for pediatric DIPG.
abstract: Treatment of pediatric diffuse intrinsic pontine glioma (DIPG) remains challenging, and reliable biomarkers of response are lacking. Radiographic response is a primary endpoint in many investigational studies of brain tumors, but there is no standard method of tumor measurement for DIPG, significant inter-observer variability exists given the invasive nature of these tumors, and tumor measurements are not predictive of outcome. Because DIPGs involve a significant portion of the pons, we evaluated the reliability and prognostic value of one-dimensional (1D) and two-dimensional (2D) pons measurements using anatomical landmarks rather than tumor boundaries. Patients with DIPG (n = 75) were evaluated longitudinally at our institution using MRI. Four readers independently performed 1D and 2D measurements of the pons using FLAIR images. Agreement and inter-reader variability were evaluated using differences among the six reader pairs and the coefficient of variation (CV). Prognostic value of pons measurements was calculated using Cox proportional hazards models, where relative hazard (RH) represents risk of death. Readers evaluated 384 exams. Agreement of readers' 1D and 2D measurements was strong (median difference between reader pairs 3.1 and 5.4%, respectively), with low inter-reader variability (median CV = 3.1% and median CV = 4.8%, respectively). Increases in 1D and 2D pons measurements over time indicated poorer prognosis (RH = 2.29, p = 0.0025 and RH = 1.13, p = 0.0016, respectively), with shorter overall survival. Pons measurements had low inter-reader variability compared to previously reported tumor measurement techniques and correlated with outcome in children with DIPG. Measurements of the pons (as opposed to direct measurements of tumor) are a viable in vivo biomarker for DIPG.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10/Room 1-5750, 9000 Rockville Pike, Bethesda, MD, 20892, USA, steffene@mail.nih.gov.
authors.forename: Emilie A
authors.initials: EA
authors.lastname: Steffen-Smith
authors.forename: Eva H
authors.initials: EH
authors.lastname: Baker
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Shaefali
authors.initials: S
authors.lastname: Shandilya
authors.forename: Robyn S
authors.initials: RS
authors.lastname: Bent
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Warren
mesh_terms: D000293:Adolescent; D020295:Brain Stem Neoplasms / Q000175:diagnosis* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D011149:Pons / Q000473:pathology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies